Evidence for a Negative Coupling between Dopamine D2 Receptors and PLC through a GTP-binding Protein, and phospholipase-A2 inhibition is devoid of effect on basal corticosteroid secretion in interrenal gland of frog Rana ridibunda

Mohamad Morra

Abstract


Dopamine D2- receptors play a pivotal role in inhibiting aldosterone secretion from adrenocortical cells. It has been demonstrated that this effect is mediated through inhibition of phospholipids turnover, although coupling of these receptors to G protein in non-mammals vertebrate has never been investigated. The aim of the present study is to shed more light on this coupling, and to demonstrate the possible implication of phospholipase-A2 activity in dopamine-evoked inhibition of corticosteroid secretion. Our present data show that the inhibitory effect of dopamine and its D2 agonists, apomorphine and LY171555 (5 µM) on inositol phosphates (IP, IP2, IP3) formation in adrenal gland (interrenal) of frog Rana ridibunda was completely abolished by a 24 hours preincubation of interrenal slices with 1 µg/ml of pertussis toxin. this suggests that dopamine D2 receptors are coupled to phospholipase-C through GTP-binding protein sensitive to pertussis toxin. In addition, dopamine had no effect on cAMP formation. However, none one of the classical dopamine D2 antagonists, i.e metoclopramide, sulpiride, and domperidone appears to be able to reverse dopamine-induced inhibition of inositol phosphate production, thus suggesting that the pharmacological characteristics of D2 dopamine receptors in interrenal gland of the frog Rana ridibunda are different from those of the D2 subtypes previously described in mammals.
Moreover, we showed that a 20-min infusion of four consecutive and croissant doses of quinacrine, a phospholipase-A2 inhibitory factor, had no effect on basal corticosterone and aldosterone secretion from interrenal slices in perifusion system. These data support the conclusion that the activation of dopamine D2 receptors is coupled to inhibition of inositol phosphate formation (inhibition of phospholipase-C activity) and corticosteroid secretion in interrenal tissue of frog Rana ridibunda occurs through a GTP-binding protein ( Gi protein), and that inhibition of phospholipase-A2 has no effect on corticosteroidogenesis.

Keywords


D2 receptors, GTP-binding protein (G protein), Inositol phosphates, Interrenal gland, Phospholipase-A2, Corticosteroidogenesis.

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